Probing the role of the protonation state of a minor groove-linker histidine in Exd-Hox-DNA binding.

ABSTRACT: DNA recognition and targeting by transcription factors (TFs) through specific binding are fundamental in biological processes. Furthermore, the histidine protonation state at the TF-DNA binding interface can significantly influence the binding mechanism of TF-DNA complexes. Nevertheless, the role of histidine in TF-DNA complexes remains underexplored. Here, we employed all-atom molecular dynamics simulations using AlphaFold2-modeled complexes based on previously solved co-crystal structures to probe the role of the His-12 residue in the Extradenticle (Exd)-Sex combs reduced (Scr)-DNA complex when binding to Scr and Ultrabithorax (Ubx) target sites. Our results demonstrate that the protonation state of histidine notably affected the DNA minor-groove width profile and binding free energy. Ex

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC10808038 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature